The development of synthetic methodology for formation of alkaloids and related compounds which have established or potential use in chemotherapy. Novel reaction steps and reaction sequences, diasteroselectivity, enantioselectivity and new reactive intermediates will be explored in order to provide practical syntheses of selected goal compounds. Structural variations on compounds with valuable biological activity are made to provide fundamental tools for structure-activity correlations and for generation of compounds with an improved therapeutic index. A new cancer chemotherapy principle, based on conformational inversions in the vinblastine class of agents, is proposed. Synthetic studies were designed to provide the required agents for this site activation chemotherapy (SAC).